The number of patients who succumb to pancreatic ductal adenocarcinoma (PDAC) each year continues to rise, unlike other leading cancers where surveillance and/or screening technologies have led to a decrease in cancer-related mortality rates (Cardin & Berlin, 2013, J Natl Cancer Inst 105:1675-6; Ma et al., 2013, J Natl Cancer Inst 105:1694-1700; Siegel et al. 2012, Cancer statistics, 62:10-29). Unfortunately, the mortality rate for PDAC is nearly equal to the incidence. The overall survival rate for all stages of pancreatic cancer diagnosed between 2001 and 2007 is only 20% after one year, and about 6% after 5 years (Siegel et al. 2012, Cancer statistics, 62:10-29). With the alarming increase in PDAC incidence, it is projected that by the year 2030, pancreatic cancer will become the second leading cause of cancer deaths in the United States (Rahib et al., 2014, Cancer Res 74:2913-21). The major reason for this poor prognosis is the inability to detect the disease at an early stage, when curative measures may have a greater opportunity to provide successful outcomes.
Biomarkers, whether they are biological, chemical, or physical in nature, have proven of significant value in providing information leading to the earlier detection and diagnosis of cancer, such as breast (Goldhirsch et al., 2003, Ann Oncol 14:1212-4), colon (Mandel et al., 1993, N Engl J Med 328:1365-71), and prostate (Jacobsen et al., 1995, JAMA 274:1445-9), resulting in improved patient outcomes. Unfortunately, this has not been the case for PDAC. Despite considerable attention directed towards discovery of biomarkers for PDAC (Lennon et al., 2014, Cancer Research 74:1-9), to date no FDA-approved means for early detection/diagnosis exists. A need exists for more effective compositions and methods for early detection and/or diagnosis of prostate cancer, preferably at the earliest stages of the disease.
In addition to more effective and earlier means of detection, a need also exists for better therapeutic treatments for pancreatic cancer. The outlook for patients with advanced pancreatic adenocarcinoma remains poor (Hidalgo, 2010, N Engl J Med 362:1605-17). In the frontline, median survival was 6.2-6.7 months with gemcitabine alone (Burris et al., 1997, J Clin Oncol 15:2403-13) or with erlotinib (Moore et al., 2007, J Clin Oncol 25:1960-6), 8.5 months combined with albumin-bound paclitaxel (Von Hoff et al., 2013, N Engl J Med 369:1691-1703), and 11.1 months for those able to tolerate combination chemotherapy (FOLFIRINOX) (Conroy et al., 2011, N Engl J Med 364:1817-25). Beyond 1st line, the survival advantage with chemotherapy remains limited (Rahma et al., 2013, Ann Oncol 24:1972-9; Oettle et al., 2014, J Clin Oncol 32:2423-9) and after two prior treatments (one usually gemcitabine-based, the other fluoropyrimidine-based), there are no accepted treatments (Seufferlein et al., 2012, Ann Oncol 23(suppl 7):vii33-40; Almhanna & Kim, 2008, Oncology (Williston Park) 22:1176-83).
There is an unmet need for more effective therapies in pancreatic cancer patients who have received and shown resistance to or relapsed from two or more prior therapies.